Abstract:
:Heat-shock transcription factor (HSF) family members function in stress protection and in human diseases including proteopathies, neurodegeneration and cancer. The mechanisms that drive distinct post-translational modifications, cofactor recruitment and target-gene activation for specific HSF paralogs are unknown. We present crystal structures of the human HSF2 DNA-binding domain (DBD) bound to DNA, revealing an unprecedented view of HSFs that provides insights into their unique biology. The HSF2 DBD structures resolve a new C-terminal helix that directs wrapping of the coiled-coil domain around DNA, thereby exposing paralog-specific sequences of the DBD surface for differential post-translational modifications and cofactor interactions. We further demonstrate a direct interaction between HSF1 and HSF2 through their coiled-coil domains. Together, these features provide a new model for HSF structure as the basis for differential and combinatorial regulation, which influences the transcriptional response to cellular stress.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Jaeger AM,Pemble CW 4th,Sistonen L,Thiele DJdoi
10.1038/nsmb.3150subject
Has Abstractpub_date
2016-02-01 00:00:00pages
147-54issue
2eissn
1545-9993issn
1545-9985pii
nsmb.3150journal_volume
23pub_type
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